: The organization of neural circuits into successive layers is a dominant characteristic of the cerebral cortex, and an understanding of how information is processed in such structures is therefore likely to give insight into the neural basis of higher cortical functions. The olfactory bulb provides a particularly attractive model for analysing this problem. Under- standing of the functional operations of bulbar circuits requires better characterization of the input to the bulb from the sensory neurons in the nose. One set of experiments will analyze the transduction of odor stimuli by olfactory sensory cells of the salamander. This work will build on ongoing analyses using whole-cell patch recordings and single channel recordings. Recent rapid advances in the analysis of second messenger systems and channel kinetics in salamander cells will be extended to the rat. Selectivity for specific odor ligands will be tested in preparations in which the proportion of cells tuned for the ligands is enhanced by retrograde labeling from projection sites in the glomeruli of the olfactory bulb. This work will test the critical hypothesis that the glomeruli are functional units which receive inputs from sensory cells with similar odor specificities. A third set of experiments, using co-cultures of rat sensory neurons and bulbar neurons, will build on current work to analyze the nature of the neurotransmitter, still unknown, that is released by the olfactory axon terminals onto their target dendrites. A fourth project will extend current studies of the physiology and pharmacology of synaptic interactions that take place within the olfactory bulb, using co-cultures of projection neurons and interneurons. Computational models will be constructed to aid in the interpretation of the experimental results and these models will be the basis of more realistic system models of the entire olfactory pathway.The results should throw light on the mechanisms involved in processing molecular information, a nonspatial modality, in contrast to the spatial information characteristic of vision and somatesthesia. The results should also improve our limited understanding of olfaction and its role in limbic functions in health and disease.